Donor hepatectomy time influences ischemia-reperfusion injury of the biliary tree in donation after circulatory death liver transplantation

Abstract

Background: Donor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. Methods: First, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportional-hazards regression analyses were used to assess the influence of hepatectomy time on the development of non-anastomotic biliary strictures. Results: Livers with severe histological bile duct injury had a higher median hepatectomy time (P ¼ .03). During normothermic machine perfusion, livers with a hepatectomy time >50 minutes had lower biliary bicarbonate and bile pH levels. In the nationwide retrospective study, donor hepatectomy time was an independent risk factor for non-anastomotic biliary strictures after donation after circulatory death liver transplantation (Hazard Ratio 1.18 per 10 minutes increase, 95% Confidence Interval 1.06e1.30, P value ¼ .002). Conclusion: Donor hepatectomy time negatively influences histological bile duct injury before normothermic machine perfusion and bile composition during normothermic machine perfusion. Additionally, hepatectomy time is a significant independent risk factor for the development of non-anastomotic biliary strictures after donation after circulatory death liver transplantation.

Ischemic Cholangiopathy Postdonation After Circulatory Death Liver Transplantation: Donor Hepatectomy Time Matters

“…Additionally, DHT has been found to be an independent risk factor associated with development of biliary complications following DCD liver transplantation. 17 With an average of <20 min, we acknowledge that the DHT in our cohort is much shorter than previous reports; however, we do not know at which point the DHT starts to have a determinantal effect on the graft. Gilbo et al 21 suggested that there is a linear relationship between DHT and IC and that there is a 19% increment in the rate of IC for every 10 min increase in DHT.…”

The Changing Landscapes in DCD Liver Transplantation

“…In a study from the UK, DHT > 60 min was associated with primary non-function (PNF) [ 32 ]. An abstract from the Netherlands demonstrated that DHT > 90 min was associated with both IC and early graft loss [ 34 ].Whether prolonged DHT is itself a risk factor, or simply a proxy for donor surgeon inexperience, is unknown. It has previously been demonstrated that transplant center standardization of organ acceptance criteria (such as donor BMI, donor age, CIT, DWIT), procurement operation (such as acceptable f-DWIT, asystole-to-cross-clamp time), and experienced procurement team help decrease complication rates related to DCD LT [ 26 ].…”

Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation

“…Recipient median (IRQ) age was 59 (53-64) years and 58 (52-63) years in the UCSF and UNOS cohort, respectively. The median MELD score was high in the UCSF cohort: 23 , compared to 18 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) in the UNOS cohort. The mean ± SD dWIT was 20.4 ± 5.9 min in the USCF cohort and 18.2 ± 7.4 min in the UNOS cohort.…”

“…Also, surprisingly, CIT did not affect the development of NAS or graft loss in our cohort. On the other hand, it seemed reasonable to think that the "tepid ischemia" caused by long dHep >60 min can irreversibly injure the graft, especially the intrahepatic bile ducts (18)(19)(20)(21). This simplified risk stratification index incorporating donor dWIT and dHep may be helpful to centers performing DCD-LT in high MELD recipients with similar local factors applying our basic DCD selection criteria (e.g., donor age <60 years, limited steatosis, no retransplantation).…”

“…In our experience, dHep can vary upon the presence of previous abdominal operations in the donor, the presence of more than one recovery team, the technique (taking the head of the pancreas with the liver (i.e., "super-rapid" technique) vs. doing the portal dissection in the cold), and the presence of anatomical variations. The increasing use of local recovery teams is another argument in favor of the timely documentation and standardization of organ extraction times, as further emphasized by others (19,20,30). In this context, many centers do not rely on local procurement for DCDs and consider the requirement for airplane travel of the DCD liver exclusion criteria.…”